crossing96/oncoscreening huggingface dataset:
Diallyl trisulfide-induced apoptosis of bladder cancer cells is caspase-dependent and regulated by PI3K/Akt and JNK pathways.	Diallyl trisulfide (DATS) is one of the major organosulfur components of garlic (Allium sativum L.), which inhibits the proliferation of various cancer cells, but the exact mechanisms of this action in human bladder cancer cells still remain largely unresolved. In this study, we investigated how DATS induces apoptosis in T24 human bladder cancer cells in vitro. Treatment of T24 cells with DATS resulted in potent anti-proliferative activity. Additionally, some typical apoptotic characteristics, such as chromatin condensation and an increase in the population of sub-G1 hypodiploid cells, were observed. With respect to the mechanism underlying the induction of apoptosis, DATS reduced the expression of anti-apoptotic Bcl-2 and Bcl-xL, and inhibitor of apoptosis protein family proteins, but the expression of pro-apoptotic Bax and death receptor-related proteins was increased compared with the controls. DATS also activated caspase-8 and -9, the respective initiator caspases of the extrinsic and the intrinsic apoptotic pathways. The increase in mitochondrial membrane depolarization was correlated with activation of effector caspase-3 and cleavage of poly-ADP-ribose polymerase, a vital substrate of activated caspase-3. Blockage of caspase activation through treatment with a pan-caspase inhibitor consistently inhibited apoptosis and abrogated growth inhibition in DATS-treated T24 cells. The study further investigated the roles of the phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) pathways with respect to the apoptotic effect of DATS, and showed that DATS deactivates Akt. Additionally, DATS activates extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK), but not p38 MAPK, in T24 cells. Unlike ERK, JNK inhibitors reversed DATS-induced apoptosis and growth inhibition; however, inhibition of PI3K/Akt notably enhanced the apoptotic action of DATS. The results suggest that the pro-apoptotic activity of DATS is probably regulated by a caspase-dependent cascade through the activation of both intrinsic and extrinsic signaling pathways, which is mediated through the blocking of PI3K/Akt and the activation of the JNK pathway.	bladder
CD40 ligand and tdTomato-armed vaccinia virus for induction of antitumor immune response and tumor imaging.	Oncolytic vaccinia virus is an attractive platform for immunotherapy. Oncolysis releases tumor antigens and provides co-stimulatory danger signals. However, arming the virus can improve efficacy further. CD40 ligand (CD40L, CD154) can induce apoptosis of tumor cells and it also triggers several immune mechanisms. One of these is a T-helper type 1 (Th1) response that leads to activation of cytotoxic T-cells and reduction of immune suppression. Therefore, we constructed an oncolytic vaccinia virus expressing hCD40L (vvdd-hCD40L-tdTomato), which in addition features a cDNA expressing the tdTomato fluorochrome for detection of virus, potentially important for biosafety evaluation. We show effective expression of functional CD40L both in vitro and in vivo. In a xenograft model of bladder carcinoma sensitive to CD40L treatment, we show that growth of tumors was significantly inhibited by the oncolysis and apoptosis following both intravenous and intratumoral administration. In a CD40-negative model, CD40L expression did not add potency to vaccinia oncolysis. Tumors treated with vvdd-mCD40L-tdtomato showed enhanced efficacy in a syngenic mouse model and induced recruitment of antigen-presenting cells and lymphocytes at the tumor site. In summary, oncolytic vaccinia virus coding for CD40L mediates multiple antitumor effects including oncolysis, apoptosis and induction of Th1 type T-cell responses.	bladder
Prospective phase II study of image-guided local boost using a real-time tumor-tracking radiotherapy (RTRT) system for locally advanced bladder cancer.	OBJECTIVE: The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique. METHODS: Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than ±2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated. RESULTS: Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65%. CONCLUSIONS: Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients' quality of life.	bladder
Induction of invasive transitional cell bladder carcinoma in immune intact human MUC1 transgenic mice: a model for immunotherapy development.	A preclinical model of invasive bladder cancer was developed in human mucin 1 (MUC1) transgenic (MUC1.Tg) mice for the purpose of evaluating immunotherapy and/or cytotoxic chemotherapy. To induce bladder cancer, C57BL/6 mice (MUC1.Tg and wild type) were treated orally with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) at 3.0 mg/day, 5 days/week for 12 weeks. To assess the effects of OH-BBN on serum cytokine profile during tumor development, whole blood was collected via submandibular bleeds prior to treatment and every four weeks. In addition, a MUC1-targeted peptide vaccine and placebo were administered to groups of mice weekly for eight weeks. Multiplex fluorometric microbead immunoanalyses of serum cytokines during tumor development and following vaccination were performed. At termination, interferon gamma (IFN-γ)/interleukin-4 (IL-4) ELISpot analysis for MUC1 specific T-cell immune response and histopathological evaluations of tumor type and grade were performed. The results showed that: (1) the incidence of bladder cancer in both MUC1.Tg and wild type mice was 67%; (2) transitional cell carcinomas (TCC) developed at a 2:1 ratio compared to squamous cell carcinomas (SCC); (3) inflammatory cytokines increased with time during tumor development; and (4) administration of the peptide vaccine induces a Th1-polarized serum cytokine profile and a MUC1 specific T-cell response. All tumors in MUC1.Tg mice were positive for MUC1 expression, and half of all tumors in MUC1.Tg and wild type mice were invasive. In conclusion, using a team approach through the coordination of the efforts of pharmacologists, immunologists, pathologists and molecular biologists, we have developed an immune intact transgenic mouse model of bladder cancer that expresses hMUC1.	bladder
Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells.	Survivin is overexpressed in transitional cell carcinoma (TCC), the most common type of bladder cancer. Previous reports demonstrated that knockdown of survivin by siRNA induced apoptosis of TCC cells. The present study evaluated the therapeutic effects of sepantronium bromide (YM155), a novel small molecule survivin inhibitor under clinical trials, on TCC cells in vitro. BFTC905, a grade III TCC cell line derived from a patient of blackfoot disease in Taiwan, was the most gemcitabine-resistant cell line when compared to BFTC909, TSGH8301 and T24 in cytotoxicity assay, resulting from upregulation of securin and bcl-2 after gemcitabine treatment. YM155 caused potent concentration‑dependent cytotoxicity in 4 TCC cell lines (IC50s ≤20 nM), but exhibited no cytotoxicity in survivin-null primary human urothelial cells. For BFTC905 cells, addition of gemcitabine and/or cisplatin, the standard TCC chemotherapy regimen, to YM155 did not exert additive cytotoxic effects. Molecular analyses indicated that YM155 inhibited the proliferation of BFTC905 cells by increasing p27kip1, suppressing Ki-67, and inducing quiescence. In addition, YM155 elicited apoptosis manifested with DNA fragmentation through suppressing the expression of survivin, securin and bcl-2. Furthermore, YM155 induced autophagy in BFTC905 cells as autophagic inhibitor, 3-methyladenine, attenuated YM155-induced LC3B-II levels and reversed the cytotoxicity of YM155. mTOR inhibitors sirolimus and everolimus did not increase YM155-induced expression of LC3B-II nor augment YM155-induced cytotoxicity. These results indicate that YM155 exerts its lethal effect on BFTC905 cells via apoptotic and autophagic death pathways and suggest that YM155 may be a potential drug for the therapy of gemcitabine-resistant bladder cancer.	bladder
Metastatic squamous cell carcinoma urinary bladder coexisting with tuberculosis in pelvic lymph nodes.	Squamous cell carcinoma (SCC) of the urinary bladder is usually associated with Schistosoma haematobium and chronic bladder irritation. We report a case of coexistent metastatic SCC and tuberculosis in obturator lymph nodes in radical cystoprostatectomy and pelvic lymphadenectomy specimens. Though tubercular iliac lymphadenitis and metastatic transitional carcinoma following intravesical BCG has been reported, the concurrent presence of non-transitional cell cancer and primary lymph nodal tuberculosis in regional lymph nodes is rare. This case is reported to highlight the paucity of management guidelines available presently in the treatment of such patients who require systemic chemotherapy and antitubercular therapy.	bladder
Transuretral resection of the bladder (TURB): analysis of complications using a modified Clavien system in an Italian real life cohort.	INTRODUCTION: To evaluate the applicability of a modified Clavien classification system (CCS) in grading postoperative complications of transurethral resection of bladder tumours (TURB). MATERIALS AND METHODS: A series of patients undergoing monopolar TURB from April 2011 to March 2012 at five Italian centers were enrolled. All complications occurring within the first 30-day postoperative period were prospectively recorded and graded according to the CCS. RESULTS: Overall, 275 patients were included. Median age was 71 (63/78) years; median BMI was 28 (25.4/30.8) Kg/m(2), median tumour size was 2 (1-3) cm; median number of tumour lesions was 1 (1-3). Median operative time was 30 (20/45) min. Fifty-seven complications were recorded in 43 patients. Overall postoperative morbidity rate was 16%. Most of the complications were not serious and classified as Clavien type I (42 cases; 74%) or II (8 cases, 14%). Higher grade complications were scarce: CCS IIIa in 1 case (2%) and CCS IIIb in six cases (10%). No TURB related death was reported. Six patients were re-operated due to significant bleeding or clot retention on postoperative days 2-7. On univariate (73.5 ± 38 versus 36.7 ± 21.6 min) and multivariate analysis longer operative time was an independent predictor of complications (OR: 1.06 per min, 95%CI 1.04-1.08, p = 0.001). CONCLUSIONS: A modified CCS can be used as a standardized tool to objectively define the complications of TURB which confirms to be a safe procedure with a low surgical morbidity. This tool can be used to aid in patient counselling and to facilitate scientific assessment.	bladder
Granular cell tumor of the bladder: a case report.	BACKGROUND: Granular cell tumor is usually a benign tumor, generally believed to be of neural origin, most commonly affecting the tongue and skin. Although it can present in any part of the body, the bladder is a rare location, with only 16 cases found in the English-language literature. CASE: We report the case of a 54-year-old woman with hematuria who had a solid tumor in the posterior wall of the bladder. Histological study of the samples obtained by transurethral resection revealed a granular cell tumor, confirmed by immunohistochemical techniques. CONCLUSION: Granular cell tumors of the bladder are rare and generally benign but frequently present macroscopic features resembling those of urothelial carcinoma. The similarity can lead to an erroneous clinical diagnosis and unnecessary, aggressive treatment. A careful histopathological assessment is essential for an accurate diagnosis.	bladder
Evolution and prognosis of bladder papillomatosis managed by endoscopic resection and endovesical BCG therapy : about 24 cases.	BACKGROUND: Bladder papillomatosis is a diffuse tumor proliferation even up almost all of the bladder mucosa. We analyzed prognosis of this rare entity after conservative treatment. METHODS: We retrospectively analyzed epidemiological, clinical, therapeutic and evolutive data in 24 patients with newly diagnosed bladder transitional cell carcinoma papillomatosis. All patients underwent a complete endoscopic transurethral resection (TUR) with curative intent. A second look was performed within 30 days. The intravesical therapy regimen consisted on weekly instillations for 6 weeks, and then monthly for 6 months. If the tumor recurred without muscle invasion, TUR was repeated with a second intravesical BCGtherapy regimen. Parameters investigated included age, gender, risk factors, cystoscopic findings (aspect, multiplicity and location of bladder lesion), tumor stage, tumor grade, recurrences and progression times from diagnosis to last follow up. RESULTS: The mean age of the patients at initial diagnosis was 64,9±6,1 years. They were males in 23 cases. Initial cancer staging was as follow: pTa (n=6) and pT1 (n=18). The recurring tumors were reported in 17 patients (70,8%). They were stage Ta in 5 patients and stage T1 in 12. The median interval of time between the initial TUR and the first recurrence was 10,3 months. Six patients remain tumor free. From the 17 recurrences, 6 patients developed progression with muscle invasion in 4 of them. Radical cystectomy with ileal conduit was performed in 3 patients and one patient died before radical treatment. Univariate analysis didn't reveal any prognostic factor: age (p=0,7), tumor location and aspect (p= 0,7 and p= 0,5 respectively), tumor stage (p=0,7) and grade (p=0,09). CONCLUSION: TCC bladder papillomatosis is a rare entity. TUR with intravesical BCG therapy may be indicated as a first option despite correct follow up. Radical cystectomy should be considered in cases of recurrent or non-resectable tumours.	bladder
Complete response of primary bladder adenocarcinoma with the FOLFOX4 regimen.	INTRODUCTION: Primary adenocarcinoma of the bladder is a very rare disease that is difficult to treat. In this paper, we report the second case in the literature with primary mucinous adenocarcinoma of the bladder which showed complete response to FOLFOX4 (fluorouracil, leucovorin, oxaliplatin) chemotherapy regimen. CASE REPORT: A 41-year-old man was admitted to our hospital with a diagnosis of primary adenocarcinoma of the bladder. Due to the similarity in histology with colon carcinoma, a FOLFOX4 regimen was started. Complete response was achieved at the end of this treatment. Today the patient is free of local or systemic disease. CONCLUSION: FOLFOX4 regimen may be a treatment option for primary adenocarcinoma of the bladder.	bladder
Prostate type epithelial polyps of urogenital tract: a series of 3 cases and literature review.	OBJECTIVE: To present clinicopathologic and immunohistochemical features of 3 cases of rare and unusual condition of urogenital tract, prostatic epithelial polyps situated in various parts of the urinary tract, with a heterogeneous presentation and a benign behavior. METHODS: Detailed data on 3 patients with polyps in the urinary tract presented from January 2008 to December 2012 were reviewed, and the clinicopathologic characteristics of the patients and disease along with various diagnostic and treatment modalities were recorded. RESULTS: All the 3 patients were aged older than 45 years. The presenting symptom hematuria was common to each patient. One patient had polypoidal growth in preprostatic (intramural) urethra; the other 2 had polyps in bladder. Each patient had other urogenital tract disease, 2 were known case of benign prostatic hyperplasia, and 1 had past history of urinary bladder carcinoma. Clinically, each of the case was misdiagnosed as aggressive lesions; however, after histopathologic diagnosis, management was undertaken according to benign result. No recurrence or metastasis was observed to date. Immunohistochemical stain prostate-specific antigen was positive in the epithelium. All 3 patients were recurrence-free on follow-up. CONCLUSION: The prostate type epithelial polyps are rare in urinary bladder and bladder urethra and are frequently associated with concurrent pathologies of urogenital tract. These are benign conditions with differential of other benign and malignant disorders.	bladder
Three-dimensional cell groups with disordered nuclei and cellular discohesion (3DDD) are associated with high sensitivity and specificity for cystoscopic urine cytopathological diagnosis of low-grade urothelial neoplasia.	Cystoscopic urine obtained before the resection of low-grade urothelial carcinoma (LGUC), with adequate cytological sampling of the tumor, frequently revealed the presence of three-dimensional cell groups with disordered nuclei and cellular discohesion (3DDD). 936 cystoscopic urine specimens were categorized into five groups: Group 1 (80 specimens) with biopsy-proven LGUC within 6 months of cytologic examination, Group 2 (23 specimens) with biopsy proven LGUC within 6 to 36 months of cytologic examination, Group 3 (527 specimens) with a history of LGUC but no tumor for a period of greater than 3 years, Group 4 (300 specimens) with no association with LGUC, and Group 5 (6 specimens) with urinary lithiasis. Specimens with scant cellularity accounted for 20% of those in Group 1. For 3DDD in detecting LGUC in adequate cystoscopic urine, the sensitivity was 70%, specificity was 94%. Two- or three-dimensional cell groups with ordered nuclei and/or cellular non-discohesion were often seen in specimens from Groups 4 or 5. The 3DDD was present in a significant number of cases with concurrent negative cystoscopic findings but also positive LGUC in ensuing follow-up. In these cases, 3DDD with or without tumor identified at concurrent cystoscopy were found to be morphologically similar. Furthermore, the presence of 3DDD in 8% of Group 3 likely represents urothelial dysplasia that is not cystoscopically detectable. The high specificity and sensitivity of 3DDD is demonstrated. These findings are consistent with the decreased cell adhesion and disordered nuclear arrangement of low grade urothelial neoplasia.	bladder
Perioperative chemotherapy in muscle-invasive bladder cancer: overview and the unmet clinical need for alternative adjuvant therapy as studied in the MAGNOLIA trial.	The European Association of Urology Research Foundation has proposed that alternatives to perioperative chemotherapy should be evaluated. The MAGNOLIA study represents a unique opportunity to investigate the concept of immunotherapy in muscle-invasive bladder cancer.	bladder
XRCC1 Arg194Trp and Arg280His polymorphisms in bladder cancer susceptibility: a meta-analysis.	The XRCC1 Arg194Trp and Arg280His polymorphisms were likely to be involved with the development of bladder cancer. However, there had been inconsistent reports of association. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, and Web of Science for relevant articles with a time limit of April 25, 2013. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association between the two polymorphisms and bladder cancer susceptibility using a random-effects model. This meta-analysis including 14 case-control studies evaluated the associations between the two XRCC1 polymorphisms and bladder cancer susceptibility. Overall, for Arg194Trp, significant associations were found in TT versus CC (OR=1.78, 95% CI=1.12-2.82) and the recessive model (OR=1.71, 95% CI=1.11-2.65); for Arg280His, significant associations were also found in AG versus GG (OR=1.63, 95% CI=1.24-2.13) and the dominant model (OR=1.39, 95% CI=1.07-1.82). When stratified by ethnicity, in Asian population, significant associations were found for Arg194Trp polymorphism in TT versus CC (OR=2.99, 95% CI=1.48-6.06), the dominant model (OR=1.33, 95% CI=1.03-1.72) and the recessive model (OR=2.72, 95% CI=1.36-5.45), and for Arg280His in GA versus GG (OR=2.13, 95% CI=1.63-2.97), but no significant associations were found in no-Asian population. This meta-analysis suggested that XRCC1 Arg194Trp and Arg280His polymorphisms were risk factors for increasing bladder cancer in Asian population.	bladder
Epigenetic inactivation of ITIH5 promotes bladder cancer progression and predicts early relapse of pT1 high-grade urothelial tumours.	Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) has been associated with tumour suppression in various cancers. However, its putative role in bladder cancer is completely unknown. Therefore, we initiated a study analysing ITIH5 expression as well as its prognostic and functional impact on human urothelial cancers (UCs). Expression analysis showed a clear down-regulation of ITIH5 mRNA in 61% (n = 45) of UCs, especially in muscle-invasive tumours (P < 0.001). ITIH5 loss in UCs was further evident on protein level (65.5%, n = 55) as detected by immunohistochemistry. DNA methylation analysis demonstrated tumour-specific ITIH5 promoter methylation in 50% of papillary none-invasive pTa (n = 30) and 68% of invasive (n = 28) UCs. Aberrant ITIH5 promoter methylation in bladder tumours was tightly linked (P < 0.001) with loss of ITIH5 mRNA expression, which was furthermore functionally confirmed by demethylation analysis in cell lines. Pyrosequencing analysis revealed that ITIH5 promoter hypermethylation was closely associated with progressive bladder cancers. Subsequently, a large cohort (n = 120) of clinically challenging pT1 high-grade UC was analysed for ITIH5 expression. Of clinical significance, we found an association between loss of ITIH5 expression and unfavourable prognosis of UC patients without distant metastasis at first diagnosis (recurrence-free survival; hazard ratio: 4.35, P = 0.048). Functionally, ITIH5 re-expression in human RT112 bladder cancer cells led to both suppression of cell migration and inhibition of colony spreading. Hence, we provide evidence that down-regulation of ITIH5 by aberrant DNA hypermethylation may provoke invasive phenotypes in human bladder cancer. Moreover, ITIH5 protein might become a prognostic biomarker for relapse risk stratification in high-grade UC patients.	bladder